Tissue Optical Clearing Devices(TOCDs)have been shown to increase light transmission through mechanically compressed regions of naturally turbid biological tissues.We hypothesize that zones of high compressive strain ...Tissue Optical Clearing Devices(TOCDs)have been shown to increase light transmission through mechanically compressed regions of naturally turbid biological tissues.We hypothesize that zones of high compressive strain induced by TOCD pins produce localized water displacement and reversible changes in tissue optical properties.In this paper,we demonstrate a novel combined mechanical finite element model and optical Monte Carlo model which simulates TOCD pin compression of an ex vivo porcine skin sample and modified spatial photon fluence distributions within the tissue.Results of this simulation qualitatively suggest that light transmission through the skin can be significantly affected by changes in compressed tissue geometry as well as concurrent changes in tissue optical properties.The development of a comprehensive multi-domain model of TOCD application to tissues such as skin could ultimately be used as a framework for optimizing future design of TOCDs.展开更多
Background: α-Synuclein is a small soluble protein,whose physiological function in the healthy brain is poorly understood.Intracellular inclusions of α-synuclein,referred to as Lewy bodies(LBs),are pathological hall...Background: α-Synuclein is a small soluble protein,whose physiological function in the healthy brain is poorly understood.Intracellular inclusions of α-synuclein,referred to as Lewy bodies(LBs),are pathological hallmarks ofαsynucleinopathies,such as Parkinson’s disease(PD)or dementia with Lewy bodies(DLB).Main body:Understanding of the molecular basis as well as the factors or conditions promoting α-synuclein misfolding and aggregation is an important step towards the comprehension of pathological mechanism ofαsynucleinopathies and for the development of efficient therapeutic strategies.Based on the conversion and aggregation mechanism of α-synuclein,novel diagnostic tests,such as protein misfolding seeded conversion assays,e.g.the real-time quaking-induced conversion(RT-QuIC),had been developed.In diagnostics, α-synuclein RT-QuIC exhibits a specificity between 82 and 100%while the sensitivity varies between 70 and 100%among different laboratories.In addition,the α-synuclein RT-QuIC can be used to study the α-synuclein-seeding-characteristics of different α-synucleinopathies and to differentiate between DLB and PD.Conclusion:The variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols,cohorts and material etc..An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical heterogeneity of α-synucleinopathies.展开更多
基金funded in part by NIH BRP grant#1R01HL098912-01by a fellowship for William CVogt provided by the Institute for Critical Technology and Applied Science(ICTAS)Doctoral Scholars Program at Virginia Tech.
文摘Tissue Optical Clearing Devices(TOCDs)have been shown to increase light transmission through mechanically compressed regions of naturally turbid biological tissues.We hypothesize that zones of high compressive strain induced by TOCD pins produce localized water displacement and reversible changes in tissue optical properties.In this paper,we demonstrate a novel combined mechanical finite element model and optical Monte Carlo model which simulates TOCD pin compression of an ex vivo porcine skin sample and modified spatial photon fluence distributions within the tissue.Results of this simulation qualitatively suggest that light transmission through the skin can be significantly affected by changes in compressed tissue geometry as well as concurrent changes in tissue optical properties.The development of a comprehensive multi-domain model of TOCD application to tissues such as skin could ultimately be used as a framework for optimizing future design of TOCDs.
基金The project was supported by the German Academic Exchange Service(DAAD)project 57421248by the Alzheimer Forschung Initiative(AFI)project 17022the Instituto Carlos Ⅲ(Miguel Servet programme—CP16/00041)to FL.
文摘Background: α-Synuclein is a small soluble protein,whose physiological function in the healthy brain is poorly understood.Intracellular inclusions of α-synuclein,referred to as Lewy bodies(LBs),are pathological hallmarks ofαsynucleinopathies,such as Parkinson’s disease(PD)or dementia with Lewy bodies(DLB).Main body:Understanding of the molecular basis as well as the factors or conditions promoting α-synuclein misfolding and aggregation is an important step towards the comprehension of pathological mechanism ofαsynucleinopathies and for the development of efficient therapeutic strategies.Based on the conversion and aggregation mechanism of α-synuclein,novel diagnostic tests,such as protein misfolding seeded conversion assays,e.g.the real-time quaking-induced conversion(RT-QuIC),had been developed.In diagnostics, α-synuclein RT-QuIC exhibits a specificity between 82 and 100%while the sensitivity varies between 70 and 100%among different laboratories.In addition,the α-synuclein RT-QuIC can be used to study the α-synuclein-seeding-characteristics of different α-synucleinopathies and to differentiate between DLB and PD.Conclusion:The variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols,cohorts and material etc..An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical heterogeneity of α-synucleinopathies.
